The Human Genome Project changed everything. A map of the entire human sequence of DNA was the starting point for an enormous number of discoveries, from disease genes to how humans evolved.
But DNA sequence is only part of the picture. Long-term, heritable changes in gene activity鈥攈ow and when each gene is turned on or off鈥攆undamentally shape our biology, trigger many of our diseases, and set the clock on how we age. While these changes can be shaped by the environment, they can also be passed down from generation to generation, in a sort of biological memory scientists are just beginning to unravel.
These heritable changes make up the 鈥攑ersistent patterns of DNA modifications that don鈥檛 alter the underlying gene sequences.
Now, two decades after the Human Genome Project, a team of University of Utah 星空传媒 scientists led by principal investigator are starting an ambitious new project to map epigenetic changes across the entire human genome. With $1.5M of new funding from the W. M. Keck Foundation, and the help of many of the original families who participated in the first map of the human genome, the team aims to discover how patterns of gene activity are inherited, track how DNA is modified as people age, and develop a comprehensive atlas of human epigenetic variation that will form an invaluable point of comparison for future studies.
Into uncharted territory
professor of human genetics and biomedical informatics in the Spencer Fox Eccles School of Medicine (SFESOM) and a principal investigator on the project, says that an epigenetics project of this scale hasn鈥檛 been done before because the technology simply wasn鈥檛 there. 鈥淭hink of the genome as the entire interstate system in the United States,鈥 Quinlan says. 鈥淭he techniques that have existed until very recently only allow us to look at the exits off the interstate.鈥 But new advances in research tests can detect chemical modifications to DNA across vast swaths of the genome, he continues. 鈥淲e鈥檙e going to study every inch.鈥
The team is especially interested in exploring how gene activity changes as people age. Here, an enormous asset is the participation of Utah families who have been involved with human genetics research for generations. In some cases, the team will be able to compare the landscape of DNA modifications for the same person across three timepoints forty years apart鈥攁n incredible resource for understanding the biology of healthy aging.
Because the families participating are large and generally healthy, the science team will be able to figure out what a 鈥渘ormal鈥 level of epigenetic variation looks like, providing a crucial point of comparison for future studies looking into how epigenetics changes with disease. And they鈥檒l be able to cross-reference DNA modifications with health conditions by integrating 25 years of electronic health records provided by the
professor of internal medicine, Huntsman Cancer Institute investigator, director of the UPDB, and a principal investigator on the project, adds that a major strength of the newly funded research is how it will bring together multiple unique resources to answer previously unsolvable questions.
"We鈥檙e going all the way from these amazing families to state-of-the-art genetics and epigenetics to the richest, deepest longitudinal health history. The data we鈥檙e going to generate blows my mind."
Rewriting risk
By working with multigenerational families, the researchers will also be able to get a better picture of which changes are inherited and which aren鈥檛. DNA modifications themselves are wiped clean when sperm and egg fuse, but are replaced in patterns that sometimes recur, generation to generation. Some of the patterns are probably caused by underlying variation in the DNA sequence itself; others are triggered by environmental factors.
How and when DNA modifications are inherited is largely unknown, says Neklason, director of the and a research associate professor of internal medicine at SFESOM. 鈥淧eople are just starting to have glimpses into this.鈥 But by comparing genetic and epigenetic information throughout participating families, the research team hopes to shed light on this mystery.
And intriguingly, because epigenetic changes can be affected by the environment, they can in theory be manipulated to improve health, says Camp. 鈥淚f we can change how DNA expresses in the genes, then that actually gives a totally new opportunity to think about how we might change somebody鈥檚 risk profile for disease and health,鈥 Camp says. The right epigenetic changes could potentially reverse someone鈥檚 inherited risk for disease.
Neklason says that the research team鈥檚 distinct, complementary skillsets鈥攈er genetics expertise, Camp鈥檚 knowledge of epidemiology, and Quinlan鈥檚 computational skills鈥攚ill be key to the project鈥檚 success. 鈥淭he coolest part is that it鈥檚 a team where we come together with completely different perspectives that will really make this work,鈥 Neklason says. 鈥淚 have huge confidence in this having a really big impact.鈥
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About University of Utah 星空传媒
University of Utah 星空传媒 provides leading-edge and compassionate care for a referral area that encompasses Idaho, Wyoming, Montana, and much of Nevada. A hub for health sciences research and education in the region, U of U 星空传媒 has a $522 million research enterprise and trains the majority of Utah鈥檚 physicians, and more than 1,670 scientists and 1,460 health care providers at its Colleges of 星空传媒, Nursing, and Pharmacy and Schools of Dentistry and Medicine. With more than 20,000 employees, the system includes 12 community clinics and five hospitals. U of U 星空传媒 is recognized nationally as a transformative health care system and provider of world-class care.
About the W. M. Keck Foundation
Based in Los Angeles, the W. M. Keck Foundation was established in 1954 by the late W. M. Keck, founder of the Superior Oil Company. The Foundation鈥檚 grant making is focused primarily on pioneering efforts in the areas of medical research and science and engineering. The Foundation also supports undergraduate education and maintains a Southern California Grant Program that provides support for the Los Angeles community, with a special emphasis on children and youth. For more information, visit